Helsinn Group and BridgeBio Pharma Announce Update to Strategic Collaboration to Develop, Manufacture and Commercialize Infigratinib in Oncology Indications in the U.S.

Helsinn gains an exclusive license to commercialize infigratinib in the U.S.

Lugano, Switzerland and Palo Alto, CA, March 3, 2022 – Helsinn Group (Helsinn), a fully integrated, global biopharma company with a diversified pipeline of innovative oncology assets and strong track-record of commercial execution, and BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio), a commercial-stage biopharmaceutical company that focuses on genetic diseases and cancers, today announced an update to their existing strategic collaboration to develop, manufacture and commercialize infigratinib for oncology indications.

Under the terms of the amended and restated agreement, Helsinn will gain an exclusive license to commercialize infigratinib in the U.S. and will be responsible for developing, manufacturing and commercializing infigratinib in oncology indications worldwide except for achondroplasia or any other skeletal dysplasias and except in mainland China, Hong Kong and Macau. BridgeBio will be eligible to receive regulatory and commercial milestone payments as well as tiered royalties on adjusted net sales from Helsinn. BridgeBio will retain all rights to develop, manufacture and commercialize infigratinib in skeletal dysplasia, including achondroplasia.

In 2021, Helsinn and BridgeBio obtained accelerated approval for TRUSELTIQ™ (infigratinib) from the U.S. Food and Drug Administration (FDA) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. Additionally, the two parties received conditional approval by Health Canada and provisional approval by the Therapeutics Goods Association in Australia for TRUSELTIQ™ (infigratinib) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement. Continued approval in the U.S., Canada and Australia for this indication may be contingent upon confirmatory trials.

Infigratinib is not FDA-, Health Canada- or Therapeutics Goods Association-approved for any other indication in the United States, Canada and Australia, and is not approved for use by any other health authority.

Giorgio Calderari, Helsinn Group CEO commented, “We are delighted to gain the exclusive license to commercialize infigratinib in the U.S. This perfectly complements our recently announced Fully Integrated Targeted Therapy (FITT) Strategy and will utilize our unique capabilities and expertise to take products through development and to patients living with cancer across the globe. BridgeBio is a great partner, and we are looking forward to continuing our relationship with them through our non-exclusive collaboration framework to propose co-development and co-commercialization opportunities for preclinical precision oncology programs.”

“We are expanding our partnership with Helsinn so that even more patients with FGFR-driven cancers will ultimately be able to access infigratinib. Focused execution means reducing the scope of our internal activity. We will continue to advance high-quality programs in our pipeline, while allowing Helsinn to develop and commercialize infigratinib in cancer indications for patients in need,” said Neil Kumar, Ph.D., founder and CEO of BridgeBio.

In March 2021, Helsinn and BridgeBio entered into a global license and collaboration agreement to co-commercialize infigratinib for oncology in the U.S. and to co-develop, manufacture and commercialize infigratinib for such indications outside the U.S., excluding mainland China, Hong Kong and Macau. BridgeBio previously entered a strategic collaboration with LianBio for development and commercialization of infigratinib in oncology indications in mainland China, Hong Kong and Macau.

In November 2021, Helsinn and BridgeBio entered into a strategic collaboration to co-develop and co-commercialize a potentially first-in-class inhibitor designed to target glutathione peroxidase 4 (GPX4), which will be investigated in patients with difficult-to-treat tumors. Alongside this, Helsinn and BridgeBio established a new non-exclusive collaboration framework agreement that allows the companies to propose co-development and co-commercialization opportunities for preclinical precision oncology programs. The terms in this strategic collaboration have not changed.

About Infigratinib

Infigratinib is a potent orally administered, selective, ATP‐competitive, kinase inhibitor of FGFRs, with highest affinity for FGFR 1, 2, and 3. The therapy is currently under investigation as a potential first-line treatment for individuals with FGFR2-altered cholangiocarcinoma (bile duct cancer) and in the adjuvant setting for individuals with FGFR3-altered urothelial carcinoma (bladder cancer). Infigratinib is also in development in skeletal dysplasias for the treatment of individuals with FGFR3-altered achondroplasia. BridgeBio retains full rights to develop and commercialize infigratinib in skeletal dysplasias for the treatment of individuals with FGFR3-altered achondroplasia.

About Cholangiocarcinoma (CCA)

CCA represents an aggressive group of malignancies that form in the bile ducts. Although rare in most countries (with a worldwide estimated incidence of <6 per 100,000 people), the incidence of this malignancy is increasing worldwide. Because the disease is usually asymptomatic at early-stages, diagnosis may be delayed until advanced stages, when CCA typically presents as locally advanced or metastatic disease. Despite continuing advances in treatments, the prognosis for this disease remains poor, with a 5-year survival rate of <20%.  FGFR2 genetic alterations are present in approximately 15% to 20% of CCA patients and represent potential targets for treatments.^1,2

U.S. Indication and Important Safety Information for TRUSELTIQ (infigratinib)

TRUSELTIQ (infigratinib) capsules 25mg/100mg is indicated for the treatment of adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

Accelerated approval was granted based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).

Warnings and precautions

• Ocular toxicity: Retinal pigment epithelial detachment (RPED), which may cause blurred vision, occurred in 11% of 351 patients treated with TRUSELTIQ, including patients with asymptomatic RPED, with a median onset of 26 days. Perform comprehensive ophthalmological exam including optical coherence tomography prior to initiating, at 1 month, at 3 months, and then every 3 months during treatment with TRUSELTIQ. Urgently evaluate patients for onset of visual symptoms and follow up every 3 weeks until resolved or TRUSELTIQ is discontinued. Withhold TRUSELTIQ as recommended. Dry eye occurred in 29% of 351 patients; treat with ocular demulcents as needed
• Hyperphosphatemia and soft tissue mineralization: Hyperphosphatemia, which can lead to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis, vascular calcification, and myocardial calcification, occurred in 82% of 351 patients treated with TRUSELTIQ, with a median time to onset of 8 days (range 1-349); 83% of 351 patients treated with TRUSELTIQ received phosphate binders. Monitor for hyperphosphatemia throughout treatment. Initiate phosphate-lowering therapy for serum phosphate >5.5 mg/dL; withhold TRUSELTIQ and initiate phosphate-lowering therapy for serum phosphate >7.5 mg/dL; withhold, reduce the dose, or permanently discontinue TRUSELTIQ based on duration and severity of hyperphosphatemia
• Embryo-fetal toxicity: TRUSELTIQ can cause fetal harm. Advise pregnant women of the potential risk to the fetus; advise females of reproductive potential and men who are partnered with women of reproductive potential to use effective contraception during treatment with TRUSELTIQ and for 1 month after the final dose

Adverse reactions

• Most common adverse reactions (incidence ≥20%, all grades): nail toxicity, stomatitis, dry eye, fatigue, alopecia, palmar-plantar erythrodysesthesia syndrome, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, blurred vision, and vomiting
• Most common laboratory abnormalities (incidence ≥20%, all grades): increased creatinine, increased phosphate, decreased phosphate, increased alkaline phosphatase, decreased hemoglobin, increased alanine aminotransferase, increased lipase, increased calcium, decreased lymphocytes, decreased sodium, increased triglycerides, increased aspartate aminotransferase (AST), increased urate, decreased platelets, decreased leukocytes, decreased albumin, increased bilirubin, and decreased potassium

Drug interactions

• CYP3A inhibitors: Avoid use with strong and moderate CYP3A inhibitors
• CYP3A inducers: Avoid use with strong and moderate CYP3A inducers
• Gastric acid–reducing agents: Avoid coadministration with proton pump inhibitors, histamine-2 receptor antagonists (H2RA), and locally acting antacids. If coadministration of H2RA or locally acting antacids cannot be avoided, separate TRUSELTIQ administration
  • H2RA: Take TRUSELTIQ 2 hours before or 10 hours after
  • Locally-acting antacid: Take TRUSELTIQ 2 hours before or 2 hours after

Dosage and administration

• Prior to initiating TRUSELTIQ: Confirm FGFR2 fusion or rearrangement; perform comprehensive ophthalmic exam including OCT; confirm negative pregnancy test in females of reproductive potential
• Starting dose: Take TRUSELTIQ orally once daily on Days 1-21 of 28-day cycles; continue treatment until disease progression or unacceptable toxicity. Take TRUSELTIQ on an empty stomach with a glass of water at least 1 hour before or 2 hours after food
  • No renal or hepatic impairment
    • 125 mg (one 100 mg capsule and one 25 mg capsule)
  • Mild and moderate renal impairment (creatinine clearance 30-89 mL/min)
    • 100 mg (one 100 mg capsule)
  • Mild hepatic impairment (total bilirubin >upper limit of normal [ULN] to 1.5 x ULN or AST > ULN)
    • 100 mg (one 100 mg capsule)
  • Moderate hepatic impairment (total bilirubin >1.5 to 3 x ULN with any AST)
    • 75 mg (three 25 mg capsules)
• Dose modification: Consult the TRUSELTIQ full Prescribing Information for dose modifications and monitoring recommendations for RPED, hyperphosphatemia, and other Grades 3-4 adverse reactions

For additional information, please see the U.S. Full Prescribing Information for TRUSELTIQ

References
¹Banales, J., Cardinale, V., Carpino, G. et al. Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol 13, 261–280 (2016). https://doi.org/10.1038/nrgastro.2016.51

² Banales, J.M., Marin, J.J.G., Lamarca, A. et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol 17, 557–588 (2020). https://doi.org/10.1038/s41575-020-0310-z